The field of 3He hyperpolarized gas MRI has seen great advances recently. This is not the case for MRI with 129Xe gas. The principal reason for this disparity is the limited supply of highly polarized 129Xe gas available for studies. For example, present day polarization apparatus for 129Xe MRI typically provide less than 1/2 liter per hour at 10% polarization. Members of our collaboration have recently demonstrated a revolutionary new polarization apparatus that operates at lower xenon pressures and higher flow velocities than existing state-of-the-art. Their results have confirmed that higher xenon polarizations can be obtained at lower operating pressures with fixed gas production rate. Thus the purpose of this BRP is to use this exciting new source of highly polarized and high throughput ]29Xe gas to explore its potential to provide quantitative information on lung structure and function. While both 129Xe and 3He provide excellent ventilation maps, 129Xe is unique in 3 ways: (1) a high solubililty in tissue, (2) a large chemical shift of the tissue relative to the gas NMR frequency, and (3) a -25 times smaller diffusion constant compared to 3He. Properties 1 and 2 permit measurement of exchange of xenon gas into tissue. We will exploit this to determine the regional surface area to volume ratio, a microstructure parameter closely related to gas exchange efficiency. A second quantity, the diffusivity of 129Xe gas in the acinus, will also be measured as a function of the time allowed for diffusion to evolve. Because of Property 3, the short time 129Xe diffusion distance is smaller than possible with 3He, probing dimensions comparable to the average alveolar pore size. At long times, D(t) gives additional information about the lung microstructure, specifically the connectivity (or tortuosity) between adjacent acinar structures. Tortuosity may be an important predictor for susceptibility to airborne particulates. We propose measurements of 129Xe D(t) to establish its value as a "fingerprint" of lung microstructure. The team of researchers assembled for this proposal have been closely collaborating for over 6 years and have developed particular expertise in both polarizing and exploiting the unique features of 129Xe. A polarizer will be built, sited and supported at Brigham and Women's Hospital. Animal and human studies are proposed to demonstrate the structural and functional information 129Xe MRI can provide.